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Bioinformatics

 

Computational Anti-Cancer Immune stimulation using Tumor Cell RNAs CAIS-TR

Manual Curation of miRNA networks and Network analysis

We have constructed a miRNA-disease network for colorectal cancer through mirnet [1] tool which integrates data from eleven other miRNA databases according to the latest update of exosomal and tissue-specific miRNAs. The constructed network [figure-1] has been analysed using cytoscape [2] for significant interaction according to the curated attributes of statistical significance. The analysis included curation of published evidence as filtering attribute in addition to statistical significance which suggested miRNAs (mir-134 and mir-370) to be of very significant connection to colorectal cancer network and by further literature research we found a potential tumor suppressor role for both RNA molecules in CRC carcinogenesis by regulating EGFR signaling cascade through targeting PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) and EGFR (Epidermal growth factor receptor) [3]. (Figure 1).

Figure 1: Colorectal cancer constructed network, analyzed using cytoscape

MiRNA-mRNA interaction networks String database [4] has been mined using RAIN tool [5] in order to construct interaction networks for both miRNAs (mir-370-3p and mir-134-5p) to be used for further pathway analysis [Figure-2, Figure-3].

Figure 2: String database interaction network of mir-134-5p and target proteins

Figure 2: String database interaction network of mir-370-3p and target proteins

Figure 2: Cytoscape constructed networks for pathway analysis of miRNAs target mRNA list

Table-1 Significant pathways enriched in miRNAs target list from KEGG database

Index	Name	P-value	Adjusted p-value	Z-score	Combined score
1	Colorectal cancer_Homo sapiens_hsa05210	0.00004363	0.002610	-1.96	19.65
2	ErbB signaling pathway_Homo sapiens_hsa04012	0.00003766	0.002610	-1.90	19.35
3	Pathways in cancer_Homo sapiens_hsa05200	0.00008735	0.002610	-2.00	18.72
4	MAPK signaling pathway_Homo sapiens_hsa04010	0.00008799	0.002610	-1.87	17.47
5	Bladder cancer_Homo sapiens_hsa05219	0.00006857	0.002610	-1.82	17.42
6	Renal cell carcinoma_Homo sapiens_hsa05211	0.00006887	0.002610	-1.81	17.36
7	Chronic myeloid leukemia_Homo sapiens_hsa05220	0.0001214	0.002701	-1.71	15.40
8	HIF-1 signaling pathway_Homo sapiens_hsa04066	0.0001108	0.002701	-1.68	15.32
9	Proteoglycans in cancer_Homo sapiens_hsa05205	0.001447	0.02575	-1.78	11.64
10	MicroRNAs in cancer_Homo sapiens_hsa05206	0.001268	0.02509	-1.72	11.44

 

Table-2 Significant pathways enriched in miRNAs target list from PANTHER database

Index	Name	P-value	Adjusted p-value	Z-score	Combined score
1	p53 pathway feedback loops 2_Homo sapiens_P04398	0.001279	0.05882	-1.66	11.04
2	EGF receptor signaling pathway_Homo sapiens_P00018	0.006002	0.1034	-1.67	8.54
3	p53 pathway_Homo sapiens_P00059	0.006743	0.1034	-1.33	6.64
4	Interleukin signaling pathway_Homo sapiens_P00036	0.01305	0.1339	-1.32	5.73
5	Angiogenesis_Homo sapiens_P00005	0.01746	0.1339	-1.18	4.79
6	Toll receptor signaling pathway_Homo sapiens_P00054	0.01494	0.1339	-1.04	4.36
7	CCKR signaling map ST_Homo sapiens_P06959	0.03086	0.2028	-1.23	4.29
8	Ras Pathway_Homo sapiens_P04393	0.03649	0.2055	-0.95	3.14
9	T cell activation_Homo sapiens_P00053	0.04202	0.2055	-0.80	2.55
10	Integrin signalling pathway_Homo sapiens_P00034	0.08346	0.2953	-0.63	1.58